Short summary

Magnetic resonance imaging (MRI) is the modality of choice for monitoring treatment response in brain tumors. However, it can be challenging to discern true disease progression from treatment-related changes on conventional MRI. We wish to investigate whether brain stiffness, measured with magnetic resonance elastography (MRE) can be used to accurately assess treatment response in a cohort of brain tumor patients.

Rationale

Brain tumors stand out among other cancers because of their high mortality compared to incidence. Gliomas are the most common primary malignant brain tumor. Distinguishing between disease progression and treatment-induced changes (pseudoprogression) can be difficult using conventional MRI because progression and pseudoprogression may appear similar. It can be equally challenging to assess response in patients treated with antiangiogenics, where treatment-induced reduction of the contrast enhancing lesion observed on conventional T1-weighted MRI with gadolinium-based contrast agents does not correspond to true reduction of the tumor. The ability to discern between true progression and pseudoprogression and to accurately assess antiangiogenic treatment response can make it easier to choose the appropriate treatment strategy, avoid unnecessary discontinuation of treatment and repeat surgery/biopsy. Moreover, the uncertainty caused by equivocal MR imaging changes and the need for follow-up scans can increase patient anxiety and potentially lead to delays in treatment.

MRE is an emerging technique which offers quantitative, non-invasive, in vivo information about brain mechanical properties with the potential to evaluate pathological processes. Brain MRE can provide reliable estimates of tissue stiffness in healthy volunteers, with coefficients of variation (CV) of less than 1% for global brain stiffness and below 10% for localized white matter structures. However, MRE repeatability and reproducibility in a patient population are less studied and need to be determined in order to understand the potential role of brain stiffness as a new quantitative imaging biomarker for clinical decisions. MRE has showed promising results in glioma imaging, where stiffness was lower in tumors compared to the healthy brain and it was shown that decreased stiffness was associated with gliomas IDH wild-type.

In patients receiving antiangiogenic therapy, MRE may be less influenced by the confounding effect of treatment-induced vasculature normalization than contrast-enhanced MRI. The use of MRE to assess antiangiogenic treatment response has been investigated in a mouse glioblastoma (GBM) model, where stiffness decrease (i.e. progression) was significantly slowed down in treated tumors compared to controls.

The overall aims of this study are:

1. To assess the repeatability and reproducibility of MRE in in a cohort of newly diagnosed brain tumor patients and compare it to an age and gender-matched group of healthy volunteers.

2. To explore the use of MRE as biomarker of response to antiangiogenic therapy for recurrent GBM.

3. To evaluate the ability of MRE to discern true progression from pseudoprogression during radiochemotherapy.

Description of the cohort

Adult glioma patients, undergoing surgery and radiochemotherapy at Odense University Hospital. Control group of healthy volunteers, age and gender-matched to the patient cohort in the repeatability/reproducibility study.

Collaborating researchers and departments

Department of Oncology, Odense University Hospital, Department of Neurosurgery, Odense University Hospital, Mayo Clinic, Rochester, Minessota, USA